Ask the CLL Expert

Ask the CLL Expert – Dr. Richard Furman

CLL specialist Dr. Richard Furman, Director of the CLL Research Center at Weill Cornell Medicine, answered patients burning questions live in this installment of Ask The Expert.

Transcript

Andrew Schorr:

And hello. Greetings. I’m Andrew Schorr in southern California, San Diego area, and I’ve been living with CLL for 22 years, so I’m vitally interested in today’s Ask the Expert session, this Patient Empowerment Network program. We want to thank PEN, as we call it, and also the financial supporters of this program, AbbVie Incorporated and Pharmacyclics, although reminding you that they have no editorial control. You’ll be hearing from our leading expert in CLL in just a minute.

Over the next 30 minutes or so we’ll get to as many questions as we can. Remember not to make it too personal. Let it help everybody in the community. And also discuss what you learn with your own CLL provider so you get the treatment that’s right for you. Okay.

Let’s meet our expert joining us from New York City and Weill Cornell medicine, and that’s Dr. Richard Furman, who is the director of the CLL research center in New York City at Weill Cornell. Dr. Furman, welcome back. Thanks for being with us.

Dr. Furman:

Thank you. It’s my pleasure. Thank you for having me.

Andrew Schorr:

Okay. We have lots of questions. One of them that somebody wants to know about is, first of all, if they’ve been‑‑maybe this is an easy one. If they’ve been diagnosed with SLL, small lymphocytic lymphoma, is that the same as CLL and what we’re talking about with CLL applies to them?

Dr. Furman:

So that’s a very important question, and this is one that I actually think is very indicative of how little we used to know. So in 1993 we actually had a diagnosis of CLL, chronic lymphocytic leukemia, and a diagnosis of small lymphocytic lymphoma. And we had patients that were diagnosed with SLL if they had a lymph node sent to the pathologist, or they were diagnosed with CLL if they had a bone marrow biopsy sent to the pathologist.

Clearly, we knew that patients could only have one diagnosis and not two, so in 1994 with the new lymphoma classification system the term was actually changed to be CLL/SLL. So they really are exactly the same entity. We don’t actually refer to differences anymore, and the whole, the whole individual‑‑the whole disease should be called CLL/SLL.

Now, an important thing is sometimes people require having a lymphocytosis to meet the definition of CLL, but the truth is both conditions are exactly the same. Both should be treated exactly the same, and there should be no difference based upon having a lymphocytosis.

Andrew Schorr:

Okay.

Dr. Furman:

Why this is most important, let me just add, is that there are sometimes people will be diagnosed with stage IV SLL and it’s very important to recognize that these stage IV SLL patients unless they have thrombocytopenia below 100,000 like the Rai stage would indicate really are not stage IV. So the lymphoma staging system would automatically make them stage IV, and that’s certainly not correct.

Andrew Schorr:

Okay. Good point. All right. Here’s a question we got in from Julia and Betty and Shelly and Mark. They all asked a similar question. They’ve been on Imbruvica for five years now with success.

Is it working for most people, and what are some reasons why it doesn’t work for everyone? And then what treatment options do you recommend if they relapse on Imbruvica?

Dr. Furman:

So right now I think the most important, there are a lot of prognostic markers available for CLL. At last count we’re probably up to 115. What’s most important is in 2018 what are those prognostic markers that really are relevant to the patient, and really as long as you stay as CLL you’re going to be able to have your disease very nicely controlled with our current agents and our novel agents.

So there are certain things that do indicate patients are likely to progress on ibrutinib, not likely progress must but who may progress, and people who might need something more, and that’s where a lot of our current clinical are research is focused. So patients who have a risk of developing a Richter’s transformation or patients who have a likelihood of developing a BTK mutation that might generate resistance to ibrutinib are the two groups of people that we worry about most.

17p deletion is probably the most important predictor for predicting those patient outcomes. There are other things that are predictive as well like having a NOTCH mutation. Those are all readily obtainable prognostic markers that allow us to determine who’s at risk and who’s not at risk for progressing on ibrutinib. If you don’t have 17p deletion or NOTCH1 mutation you have almost a 99 percent chance of being free from progression at five years on ibrutinib. And it looks like most of the people who are going to progress will progress within five years. So I think making it to that five‑year mark is really very‑‑is the most important thing.

Andrew Schorr:

Okay. So if you do progress, what then?

Dr. Furman:

So fortunately we have a lot of great agents.

Venetoclax works very effectively in patients who progress on ibrutinib, generates some very, very deep responses and very long‑lasting responses. So that’s certainly one option. Another option is to be treated with a PI3‑kinase inhibitor. So we have idelalisib and duvelisib now approved. We will shortly have umbralisib approved as well as a novel agent. We also have a whole array of other agents coming down the pipeline looking specifically at means for progression on venetoclax. So we have an MCL1 inhibitor which targets the protein that’s likely responsible for resistance to venetoclax. So all these things are actually currently in clinical trials and certainly will hold a great deal of promise.

Andrew Schorr:

Okay. Here’s a question we got in from Jeff. He says, for young and fit patients with relapsed disease what are the best combos now and coming. And I suspect maybe Jeff had received FCR, so if he relapses after FCR, what about that?

Dr. Furman:

So my belief is that these novel agents should always be used up front, or if you’ve gotten chemotherapy up front they should be used immediately at relapse. A lot of patients and physicians have the idea that there’s a benefit to holding back until you really need something, but I believe putting our best foot forward first is always the best approach. So I always recommend going forward first with BTK inhibitor therapy, followed by venetoclax or venetoclax followed by BTK inhibitor therapy. And I think so in a patient who has relapsed after FCR it will be ibrutinib or acalabrutinib. In a patient who has relapsed after acalabrutinib and ibrutinib would then move on to venetoclax.

Now, what I’m really very excited about is the possibility of the combination of either BTK inhibitor therapy plus venetoclax or PI3 kinase inhibitor therapy with venetoclax.

You know, both of these combinations really take advantage of the synergy that happens when you take a BCR antagonist like ibrutinib, acalabrutinib or idelalisib and duvelisib and combine it with a Bcl‑2 inhibitor. And it really sort of enables us to get very, very deep remissions with actually as short as just 12 months of treatment. And so those are what we’re currently testing in patients right now and what I hope will be the frontline treatment for patients in the not‑too‑distant future.

Andrew Schorr:

Now, one of the things people wonder about is if you take these big guns and put them together could you, like you’ve been able to do with FCR, stop treatment or take a break from treatment at some time.

Dr. Furman:

So I’m a big believer in that if something’s working and you’re tolerating it well that we shouldn’t mess with it, but we are currently studying two different processes with relationship to the ibrutinib plus venetoclax combination. So we’re taking patients who become MRD negative on the combination after 12 months and randomizing them to either just get ibrutinib or to get placebo. And so that’s going to give us information as to whether or not it’s safe to stop patients on the combination and treat them with nothing long term. We’ll see, one, how many patients relapse, and hopefully none, and, two, if they do relapse whether or not we can then restart ibrutinib and control their disease. So this will provide us that important question as to whether or not we’re giving up something by discontinuing the therapy.

We’ll have as our comparative those patients who got ibrutinib plus venetoclax for 12 months and then just remained on the ibrutinib.

And so that will sort of be the patients who will continue on with their therapy, and then the other half will be patients who have discontinued all their therapy.

My belief for going to venetoclax is that you’re going to get almost all of the bang for your buck out of the first 12 to 24 months, so continuing it is unlikely to yield an additional benefit, so I think stopping it is safe. But, once again, these are the studies that will provide us with those data.

Andrew Schorr:

Okay. Now Maureen sent in a question where they responded to venetoclax and rituximab and they wondered what about testing for minimal residual disease? They don’t have any lymph nodes or anything, but is that then appropriate to do a MRD test to see how deep the remission is?

Dr. Furman:

So the real important question should be whether or not that’s going to impact upon clinical management.

So MRD testing is easy, it’s noninvasive, it’s a peripheral blood test or a bone marrow biopsy, which I guess is only relatively noninvasive, and the information though is really not going to be of use. So if you’re taking a patient who’s on ibrutinib and you’re going to continue the ibrutinib knowing the MRD status won’t change anything. Likewise, if you have a patient who’s on venetoclax, who’s going to get a year of venetoclax on trial and then stop, knowing the MRD status won’t change anything as well. So currently there’s no real reason for doing MRD assessments in patients except for just the ability to know.

Now, one day there’s some modeling that suggests that the time it takes you to reach MRD negativity is half the time you need to be on a substance, an agent, before you can actually claim to have a deep enough remission that you won’t relapse. So we may one day say if you’ve been on ibrutinib for five years and became MRD negative, then 10 years of ibrutinib is enough and you can stop. But that’s currently just theoretical and based on mathematical models.

Andrew Schorr:

Theresa wrote in, she said, my husband is being treated with acalabrutinib for five months. He’s doing well, but should he have some sort of testing to know whether he will develop some sort of resistance in the future?

Dr. Furman:

So that’s a very important question, and the answer really is, you know, testing for it now isn’t going to be able to change anything. Right now we would still continue the acalabrutinib until we see signs of clinical progression. There’s some early data emerging from Ohio State where they’re doing PCR testing on all the peripheral blood of patients, on the peripheral blood of all patients to see whether or not they can detect any of these mutations that lead to resistance. The problem is you’re still going to continue the treatment until you see the clinical relapse.

And, two, is you really‑‑you know, in essence when you look at the data that suggests that 92 percent of patients who get ibrutinib as a first‑line therapy will remain in remission at five years you’re talking about treating‑‑or testing a lot of people for very, very few people that will likely benefit.

Andrew Schorr:

Okay. So if you have a question now, send it in, cll@patientpower.info, and we’ll do our best to pose it to Dr. Furman. Okay.

So Beth with wrote in and wanted to know is there work going on on a CLL vaccine?

Dr. Furman:

So we’ve been playing with CLL vaccines for at least the past 25 years, and a lot of these vaccines were originally designed to be what we call antiidiotype, meaning they were directed against the antibody made by the cell itself. Unfortunately, a lot of those vaccines have not proven effective, and we’ve gone through a lot of different iterations. We’re still trying, and hopefully one day we will have better success.

Right now a lot of our current research is focused on not so much the target that the vaccine should be against but ways to make the vaccine more effective. Things like using PD‑1 inhibitors, which can actually make the tumors more apparent to the immune system. Or using things that can actually enhance the presentation of the actual vaccine to the immune system, and that includes everything from idelalisib and ibrutinib to other different molecules that may actually make it more readily apparent.

Now, we do also have some new targets like ROR1, which may prove to be very exciting and interesting, but this is still all very far away from anything that will be approvable.

Andrew Schorr:

Okay. Now, here’s a question we got in from Cerisa, said, my understanding is that most drugs aim at destroying the CD20 protein like rituximab or obinutuzumab, etc.

Well, what about, CD9, CD15, CD23? Are they not as bad as CD20 in CLL?

Dr. Furman:

So the thing that’s really important to keep in mind is only our monoclonal antibodies attack one protein in particular, and so we have obinutuzumab, rituximab, and ofatumumab all of which address or target CD20. CD20 was the first protein targeted for two reasons. One is it’s ubiquitously expressed on all B‑cell lymphomas, and so it’s a way to identify a target that we can actually generate one treatment for that will work in a large number of people.

The second is it’s a protein that doesn’t seem to actually get endocytosed or down modulated so that it remains positive in the cases most of the time. One of the problems with some of the other proteins you mentioned is that they’re not expressed on the CLL cell.

So CD3, CD15, those are not present on CLL cells, but they’re also present on a lot of other cells as well. The key about CD19 and 20 is that they’re only on B‑cells, and we really can actually do okay without our B‑cells. And so that way the down side to knocking an out all our B‑cells is actually relatively minor. And the CAR‑T cells, which are T‑cells taken out and reprogrammed, they’re reprogrammed to be directed against CD19 and 20, so in a way they work like the monoclonal antibodies.

Andrew Schorr:

Okay. Lynn wrote in and asked about transplant in CLL, and I’ve met people who have had transplant, so where does transplant fit in now, and does CAR‑T cell experimental therapy maybe supersede that?

Dr. Furman:

One well, one of the things that’s important to keep in mind is that CAR‑T cells are still very novel, and the long‑term efficacy is not yet there, so we still need to do a lot of work to help that.

My belief is allogeneic transplants are very effective but they’re also very toxic and dangerous, and I do believe that they should be avoided if at all possible. So I am very, very selective in who I refer for allogeneic transplant.

With our novel agents like ibrutinib, idelalisib, duvelisib, umbralisib, acalabrutinib, vecabrutinib, zenabrutinib, the list is just rapidly growing, I almost believe that the patient who really needs an allogeneic transplant will only be those patients who have developed or are at high risk of developing Richter’s transformations. So I really do believe there’s a very limited role for allogeneic transplant at this point in time.

Andrew Schorr:

Okay. And CAR‑T, you’re watching it.

Dr. Furman:

I am.

Andrew Schorr:

Okay. Here’s a question that came in from Mike, and this is the bottom line for a lot of people when they’re diagnosed, and he says, what is the current state of treating CLL for those of us watch‑‑he says wait and see patients or watch and wait. In other words, is it curable?

Dr. Furman:

So right now CLL is not curable. The way that I would love everyone to start approaching CLL is very analogous to high blood pressure. So we don’t cure high blood pressure, but if you take a pill a day it’s not going to have an impact on your longevity. And I believe we’re there for about 75 to 80 percent of CLL patients, where they will be able to get a BTK inhibitor or a Bcl‑2 inhibitor or a combination and they will be able to not have to worry about their CLL for the rest of their lives.

There’s still the 20 percent who are going to develop either a Richter’s transformation or a progression on ibrutinib, and those are people we’ve got to figure out what to do differently for. But all the others, even though it’s not curable, we can definitely I think keep it from having an impact on longevity.

People on watch and wait who are high risk of progressing and developing a Richter’s or progressing onto developing resistance to ibrutinib, we do have a couple of trials that are very interesting right now where we’re treating people at diagnosis with BTK inhibitors with the hope, because they’re so well tolerated and because they’re so effective, we might be able to have an impact and prevent those patients from developing resistance or developing a Richter’s transformation.

Andrew Schorr:

Wait a minute. So are we looking at what has been the traditional watch and wait period differently now and some people will be treated much earlier?

Dr. Furman:

Well, we’re just starting to look at that right now in clinical trials. So this is very early. It’s for a very select group of people.

We know from the data‑‑so we have seven‑year data coming out at ASH this year where we’re going to have a group of people who were watched and waited and only when they had evidence of disease progression and needed treatment and got ibrutinib, 92 percent of them were still doing well and free from progression at seven years. So for those 92 percent of patients we couldn’t do any better. So it’s really just a very small group of patients who need something extra.

So, yes, we’ve proven I think in a large number of patients that BTK inhibitor therapy might be all that’s necessary, but in everyone else, in those 8 percent we do have studies going on to try to answer how to treat them differently.

Andrew Schorr:

Okay. So we got a question early on about somebody who was asking about should he be taking a statin along with his oral therapy for CLL. So people have other conditions. So what about that?

Dr. Furman:

So if you have hyperlipidemia you should definitely be on a statin, otherwise, no, you don’t need a statin. I think it’s important to keep in mind that there was a lot of data generated at one point about statins perhaps changing the CD20 expression on the surface of the CLL cells or making rituximab or other anti‑CD20 antibody therapy more efficacious. I’m not aware of any data that suggests there’s an impact to statins on non‑anti‑CD20 therapy efficacy, and I think the impact on anti‑CD20 antibody efficacy is actually really quite small and unlikely to generate a significant difference. So I really don’t believe there’s a need to do anything outside of just treating your lipids.

Andrew Schorr:

I promised our audience weeks ago that I’d ask you about this. So should we have flu shots? Should we have the shingles vaccine?

Dr. Furman:

So, absolutely. Everyone should definitely get a flu shot each year. And it’s important to get the flu shot each year because the immunity doesn’t persist. So I actually recommend people get vaccinated either October or early November. All right? So any earlier than that I worry that you’re going to have your immunity peak before the height of the season, and later than that you may not actually have sufficient time to respond.

Regarding the shingles vaccine, so there’s a new shingles vaccine called Shingrix which is a recombinant vaccine, so it’s not a live vaccine, and that’s how it’s different than the previous shingles vaccine. The previous shingles vaccine was an attenuated or live virus vaccine, and CLL patients really shouldn’t have taken it because it really theoretically could have caused shingles.

Now, the old shingles vaccine was also not very effective, so even though the risk was low with low efficacy there’s really no risk/benefit assessment that puts it in favor of doing.

But the new shingles vaccine actually has been tested in patients post autologous bone marrow transplants, so it’s very effective in patients who are very immunosuppressed, and because it’s not a live vaccine it is safe. So I do recommend it for everyone.

Andrew Schorr:

Okay. Dr. Furman, so you mentioned it earlier and we’ve heard about a lot of programs, the 17p deletion and I almost think of it as the dreaded 17p deletion, but is that necessarily true? Pam wrote in, she said, I have the 17p deletion. What are my options? So first of all, are all 17ps alike, and then what are the options?

Dr. Furman:

So the thing that’s most important to keep in mind when we talk about prognostic markers is they’re really just surrogates for clinical behavior. And so the answer always is going to be if you have historical data that’s always going to trump the prognostic marker.

So someone who is 17p deleted and their disease has remained stable for the last five years, their disease is stable, and the 17p deletion is not going to be what drives the prognosis. I think that’s very important because when you look at a curve you’re going to see some people doing well and coming off the curve late and some people doing poorly coming off the curve early. You know, where they are on the curve we have no idea how to predict. All we know is that they’re on a particular curve. So prognostic markers tell us about the population, never about the individual.

Now, with that being said, we do know 17p deletion a lot of it, the percentage of the deletion if you’re above 20 or below 20 does have an impact on how you do overall. So 20 percent and below, they‑‑patients seem to have a better prognostic outcome than the patients who have 20 percent and above.

With that being said, I do have patients who have 17p deletion in 70 percent of their cells and they’re just hanging out doing quite nicely. So clinical behavior does trump everything else.

Andrew Schorr:

Okay. So, obviously, most CLL patients are older. I’m 68 now, but I was diagnosed at 45, which is pretty young, but here’s Matthew who writes in he was diagnosed at age 31 and he wonders, he knows a lot of the statistics but he knows it’s mostly older people. He’s trying to figure out, well, what’s his life going to be like. So what do you say to younger patients with CLL today?

Dr. Furman:

So, remember, we’ve only had these novel agents since 2010, and so what I really do believe is that we really don’t know how good things are going to be yet. I think things are going to be a lot better than we ever envisioned, so I am quite optimistic about the future.

We don’t know whether or not a 31‑year‑old could enjoy a normal long life expectancy but if they don’t have evidence of or suggestions that they’re going to have particularly aggressive disease and develop resistance to a BTK or a Richter’s transformation, they could theoretically have 40 years on a BTK inhibitor. And so that’s certainly what my hope is for the future.

You know, all the survival curves that people talk about and all the survival curves that people show really don’t take into account any of the novel agents, and that’s always very important to keep in mind. So we do some have data. As I mentioned, the seven‑year data is coming out from‑‑will be out at ASH, and the seven‑year ibrutinib data really suggests almost a nearly flat curve for patients with CLL who get ibrutinib as a front‑line treatment.

Andrew Schorr:

So you mentioned over the years the Rai staging system, and Dr. Rai, the grand old man of CLL.

So how does that apply now? You know, somebody’s diagnosed with CLL, they come across this Rai staging system, but is that meaningful for them today, or are there new ways of looking at it?

Dr. Furman:

So the Rai stage really still drives when we’re going to treat patients. So patients are still treated based on meeting, you know, the classic indications for initiation of therapy. So Rai stage 3 and 4, namely hemoglobin less than 11 or a platelet count less than 100,000, really are the two primary reasons why people initiate therapy. We know that if you watch and wait someone until they meet classic criteria and they have disease that doesn’t harbor one of these high‑risk changes we know that they’re going to do extremely well. So that’s good news. Whether or not patients who have these other markers should be treated before they have aggressive disease is on open question.

Now, what I really do think that’s also important to keep in mind is, you know, the watch and wait ideology really came about when we had therapies that were not very effective and also were quite toxic. Now that we have these novel therapies that are far less toxic and highly effective, maybe the bar should move towards initiation of therapy sooner, but that’s still on open research question and not one that we know the answer to yet.

Andrew Schorr:

Okay. And Bob has had the same treatment I’ve had. He had Gazyva or obinutuzumab with high‑dose methylprednisolone, and now that was, gee, about two years ago, and now his CLL has started to show up in his spleen and his lymph nodes. He said, well, can he be treated with the same combination again, or might he move to something else?

Dr. Furman:

Well, that’s going to depend on a lot of factors. Most importantly is whether or not there was, you know, he had received the full dose in which case the likelihood is that with just a two‑year remission I would expect that retreatment would generate a shorter remission this time, and the risks associated with high‑dose methyl prednisolone plus obinutuzumab probably don’t outweigh, or aren’t going to be‑‑the risks are going to outweigh the benefits that would be gained if we’re talking about a response that’s going to last less than two years. So it would probably be better to move on to additional agents. And, fortunately, we have so many others that I think it would be a way to avoid resistance and also develop‑‑avoid, actually, the toxicities associated with high‑ dose methylprednisolone.

Andrew Schorr:

Okay. We’ll take just a few more questions, and thank you, Dr. Furman, for sticking with us. And I relate to this one. So I did have the obinutuzumab and rituximab years ago, and I developed sort of a history of sinus infections for a while and even some chest congestion and I’ve seen other people write in about it.

Do we have the sinus or the respiratory issues from the CD20 antibody or is it something else?

Dr. Furman:

So it’s important to recognize that CLL patients, 75 percent of CLL patients will develop hypogammaglobulinemia, and that hypogammaglobulinemia is probably most of the cause of the chronic sinusitis, chronic bronchitis, sort of that‑‑those issues with having the constant drainage. So I do believe that CLL in and of itself is certainly the first factor that impacts upon that.

The anti‑CD20 by itself will also cause a lot of those problems as well, so the two together are just a double hit. But we do know that CLL patients, totally regardless of their prior‑‑regardless of their prior treatments will run into those issues.

Now, with that being said, what people often forget is the most common cause of a chronic sinusitis in anyone, even a CLL patient who’s gotten obinutuzumab, is still going to be a deviated septum, or it’s going to be a blocked sinus channel, so I always recommend and I always insist on all my patients being evaluated by an ear, nose and throat doctor first just to make sure there isn’t something anatomical that could be fixed.

Andrew Schorr:

I went to an ENT the other day, and also I’ve been doing‑‑and I know my Dr. Kipps here is urging me, I’m doing the nasal wash and all that stuff, just trying to have sinus hygiene, if you will, working on that.

Okay. Couple more questions. Aukie wanted to know, and we’ve talked about this in the CLL world forever, should he be taking a green tea extract? Is there any validity for that? What do we know?

Dr. Furman:

So my belief is no. I think it’s important that we have a lot of alternative medicines, medicines that have been studied, and until they show evidence clinically I do believe that it’s important to actually stay clear of them, and there are a couple of reasons why.

So a lot of things work in the laboratory, but that doesn’t mean they’re going to translate into working clinically. And a lot of the medications that are sold as alternative medications or homeopathic medicines are unregulated and can make claims that aren’t substantiated, but they also don’t have their products necessarily vetted. So we’ve had a number of examples of people who have been taking a root or have been taking some leaf that’s turned out to be laced with amphetamines. So a leaf that claims to enhance your energy output, absolutely, if it’s laced with amphetamine will certainly be able to accomplish that.

So it’s important to keep in mind that anything that’s made naturally or that occurs naturally doesn’t actually get regulated the same way as pharmaceuticals. There was also a change in the laws in the 1990s where anything that was natural didn’t have to be tested and approved by the FDA, so the claims that they make‑‑like Tony the Tiger can say that Frosted Flakes are great without proving that in a randomized controlled clinical trial. Because it’s a naturally occurring substance it can make claims that aren’t necessarily substantiated. I do worry about that. And there are some definite cases of patients coming to harm from taking medication‑‑from taking supplements that weren’t well regulated.

Andrew Schorr:

So, as you know, so many of us complain about fatigue with CLL. What can we do about that? Is there any medication or something you feel comfortable about as a supplement that could help with that? Certainly, we’ve been telling people exercise is a good thing and can give you more energy, but what do you tell your patients when they talk about fatigue?

Dr. Furman:

So this is actually a very common question, and I really do believe it’s very important to remember that having CLL doesn’t protect you from the things that befuddle the rest of us. So the most common cause of fatigue in a CLL patient is not going to be the CLL but it’s going to be the same thing that befuddles the rest of us. So it’s poor sleep hygiene. It’s not sleeping long enough. It’s all those things that really should be addressed first and foremost. So we see a lot of sleep apnea that’s undiagnosed. We see a lot of people who are just not sleeping long enough.

If we’ve ruled out everything else and a patient seems to have progressive disease, yes, there are definitely patients with CLL whose fatigue is related to the CLL, but I’m a big believer that fatigue related to CLL should only be present in a patient who really has active signs of CLL. So if someone is on watch and wait and their lymphocyte count is not changing and their lymph nodes are not enlarged, their fatigue is not going to be related to their CLL.

But if someone’s lymphocyte count’s climbing and their lymph nodes are growing then certainly their fatigue might in part be related to their CLL.

Andrew Schorr:

Okay. This has been like being on a game show. I keep throwing things at you. I want to thank you for all your time.

Folks, we’re going to let Dr. Furman go, but we will be doing other Ask the Expert sessions and doing some live broadcasts in from ASH. ASH, you alluded to, Dr. Furman, always has more coming out, more longer range studies, combination information. So just to wrap up with, for those of us living with CLL, and, thank god, so many of us long term, me, 22 years, are you very hopeful that you have more options for us now no matter what our CLL situation is?

Dr. Furman:

I really do. I think we have some amazing options now. We have also the data that our current crop of novel agents really can be safe and effective long term, and that’s what I really think is so important to be cheerful about.

And in those patients who do progress we have a whole crop of other agents that will prove to be hopefully effective in those situations. But I think it’s going to be the‑‑you know, the home run though is going to be the combination of BTK and Bcl‑2 inhibitor therapy or PI3 kinase and Bcl‑2 inhibitor therapy because in those situations I really do see patients getting very, very deep remissions that I hope will be extremely long lasting.

Andrew Schorr:

Think about it, folks. I mean, I got FCR, a three‑drug combination, in 2000, 18 years ago, and it worked for a long time. So the idea of combination therapy has worked well in cancer therapy hitting those cancer cells in multiple ways. Dr. Furman, thank you so much for being with us today.

Dr. Furman:

My pleasure.

Andrew Schorr:

Okay. From Weill Cornell.

And I just want to mention for our audience, remember we’ve got a lot coming up. On Wednesday, November 28, we’re going to understand the ins and outs of watch and wait for those of you who are in that situation. From the big ASH meeting in San Diego‑‑yay, I don’t have to get on a plane to go anywhere‑‑we’ll be also doing live broadcasting so be sure to be signed up for that.

And then on December 5th we’re going to talk about the financial issues because, as Dr. Furman talks about, combining these oral therapies, these are expensive, and so what support is there for you so you get the combination should you need it and it’s affordable. So keep an eye on that. Go to the Patient Empowerment Network’s website, powerfulpatients.org, and take a look at what we have on Patient Power as well. Thank you so much, Dr. Furman. Thanks to our audience and stay tuned for what comes out of the ASH meeting. I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.

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